Target Attainment of TDM-guided Infusion of Piperacillin/Tazobactam and Cefepim in Critically Ill Patients

Central Hospital, Nancy, France99 enrolled

Overview

Although alternative dosing strategies can improve antimicrobial exposure in critically ill patients, the high PK variability in this population means that some may still receive sub-optimal antibiotic exposure leading to unfavourable clinical outcomes. Therapeutic drug management (TDM) guided dosing is the only safe and effective way to ensure that all critically ill patients achieve therapeutic antimicrobial exposures and to minimise the likelihood of toxicity. For experts, TDM should be a standard of care, in particular for β-lactams. Nevertheless, because of the assay method for β-lactams and the need for bioanalytical experts, delays in obtaining results frequently occurred. These barriers, combined with difficulties in the interpretation of TDM results, need to be addressed in order to increase its routine utilization. Consequently, study aiming at identify which subgroup of patients or infection are more likely to benefit from TDM are urgently warranted This prospective observational study aimed at evaluating target attainment of piperacillin/tazobactam (PIP/TAZ) and cefepim (CEF) with the use of a Therapeutic Drug Monitoring (TDM) in critically patients during the routine care

Study Type

OBSERVATIONAL

Enrollment

Conditions

Critical Illness Antibiotic Toxicity Sepsis Septic Shock

Interventions

Outcomes

Primary Outcomes

to determine the percentage of patients who met the PK/PD targets at 24 hours

PK/PD target was defined as follows: Concentration of piperacillin or cefepim between a lower and a upper limit: * The lower limit was defined as estimated free concentration above 4 times the epidemiological cut-off value of suspected bacteria * The upper limit was based on known limit of neurotoxicity, namely 35 and 160 mg/L for cefepim and piperacillin, respectively Consequently : * for piperacillin : the PK/PD target is considered to be reach if the free concentration of PIPERACILLIN/TAZOBACTAM is between 32 and 160 mg/l * for cefepim : the PK/PD target is considered to be reach if the free concentration of CEFEPIM is between 4 and 35 mg/l

Time frame: Day 1

Secondary Outcomes

to determine the percentage of patients who met the PK/PD targets "exposure" at 24 hours

PK/PD target "exposure" take into account only the the lower limit was defined as estimated free concentration above 4 times the epidemiological cut-off value of suspected bacteria Consequently : * for piperacillin : the PK/PD target is considered to be reach if the free concentration of PIPERACILLIN/TAZOBACTAM is above 32 mg/l * for cefepim : the PK/PD target is considered to be reach if the free concentration of CEFEPIM is above 4 mg/l

Time frame: Day 1

factors associated with target attainment at day 1

effect of age on antibiotic concentration